title: Hepatogenic engineering from human bone marrow mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture.
abstract: Bone marrow mesenchymal stem cells (MSCs) are promising candidates for cell therapy and tissue engineering. We used mesenchymal stem cells from human bone marrow (hMSCs) as the seeding cells to investigate the potential of hepatocytic differentiation of hMSCs in porous polylactic glycolic acid (PLGA) scaffolds under perfusion induction. hMSCs were seeded and proliferated in PLGA scaffolds, and then induced into hepatocyte-like cells with hepatogenic medium in perfusion and static cultures. The results showed that hMSCs could be induced into hepatocyte-like cells in PLGA scaffolds with hepatogenic medium in both static and perfusion induction systems. However, perfusion induction was more effective for cellularity in PLGA scaffolds than in static induction. Cells in the scaffold induced by the hepatogenic medium expressed hepatocyte-specific genes cytokeratin 19 (CK19), α-fetoprotein (αFP), cytokeratin 18 (CK18), albumin and cytochrome P4503A4 (CYP3A4) in a time-dependent manner. Induced cells stained positive for αFP and albumin. Induced cells also acquired the functional characteristics of hepatocytes, i.e. secretion of urea and albumin. In a comparison of survival and hepatogenic differentiation of hMSCs between perfusion and static induction, perfusion induction increased the survival and the uniform distribution of induced cells in scaffolds, which resulted in a higher efficiency of hepatogenesis in the PLGA construct with hMSCs. The oscillatory perfusion induction system combined with the hepatogenic medium should be a valuable and convenient tool for in vitro hepatic tissue engineering using hMSCs.
authors.affiliation: Laboratory of Stem Cells, Institute of Cell Biology, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. wjfu@zju.edu.cn
authors.forename: Jinfu
authors.initials: J
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Zong
authors.forename: Dongyan
authors.initials: D
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.forename: Liyue
authors.initials: L
authors.lastname: Liu
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Tong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zheng
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
mesh_terms: D000418:Albumins / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry*; D008099:Liver / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009991:Oscillometry / Q000379:methods; D010477:Perfusion; D010641:Phenotype; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000418:Albumins; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D004247:DNA